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The sham effect in renal denervation is dramatic and under studied as an entity itself largely because there have been so few sham controlled studies in renal denervation and device technology does not easily lend itself to sham treatments. Due to its non-invasive technology, the Wave IV study performed by Kona Medical represents an excellent opportunity to study the effect of a sham treatment in a hypertension study. The top level data from the Wave IV trial showed a trend toward greater blood pressure improvement in the sham group than in the treatment group for both ambulatory blood pressure and office blood pressure.
A subgroup analysis was performed on the full wave iv dataset. Subgroups included an analysis of the time based learning curve as the trial proceeded, age, bmi, pulse pressure, stability of the run in period, baseline blood pressure, type and quality of sedation, and power levels.
The office blood pressure (obp) drop in the sham and treatment groups respectively for all patients at 3 months was 20.4 (sd 22.3) and 16.3 (sd 17.5). The ambulatory blood pressure (ABPM) for all patients in the sham and treatment group respectively at 6 months was 8.2 (n=25, sd 16.3) and 7.2 (n=27, sd 12.8). In the subgroup with pulse pressure <65, obp in the sham and treatment groups at 3 mos were 12.7 (n=9, sd 20.1) and 31.7 (n=8, sd 31.7) respectively and ambulatory BP in the sham and treatment groups was 8 (n=5 sd 16.6) and 19 (n=7 sd 19.4) respectively. In the subgroup of patients who were stable in the run in or who had a pulse pressure <65, obp drop was 15.6 (n=22 sd 13.5) and 19 (n=25 sd 21.7) in the sham and treatment groups respectively. ABPM drop at 6 mos was 2.8 (n=15 sd 11.6) and 9.8 (n=18 sd 15.6) in the sham and treatment groups respectively.
These data are intriguing and hypothesis generating. Specific subgroups may have a greater propensity toward being sham responders. Perhaps patients with the most unstable and volatile blood pressures are also most likely to have a sham response. These data show that patients with stable run in and with lower pulse pressure have a smaller sham effect. Subgroup selection for future studies may be more about minimizing sham effect than maximizing the absolute treatment effect. Treatment optimization could be called sham effect minimization strategies.
ENDOVASCULAR: Peripheral Vascular Disease and Intervention